Modulation of Naturalistic Maladaptive Memories Using Behavioural and Pharmacological Reconsolidation-interfering Strategies: a Systematic Review and Meta-analysis of Clinical and 'sub-clinical' Studies

Background: Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This represents a potentially transformative strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, modulation of naturalistic maladaptive memories may be limited by 'boundary conditions' imposed on the reconsolidation process by the nature of these memories.

Methods: We conducted a systematic review and meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward- and threat-related memories in (sub) clinical substance use and anxiety/trauma, respectively.

Results: Of 4938 publications assessed for eligibility, 8 studies of substance use and 10 of anxiety (phobia)- and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with most studies favouring the 'retrieval + treatment' condition. However, the magnitude of effects was dependent upon the nature of treatment, with pharmacological interventions showing a medium-sized effect (g = 0.59, p = 0.03) and behavioural treatments, a relatively small effect (g = 0.32, p = 0.10) in studies of phobia/trauma. Among studies of substance use, post-retrieval behavioural interventions yielded a larger effect (g = 0.60, p < 0.001) relative to pharmacological treatments (g = - 0.03, p = 0.91), with treatment type being a statistically significant moderator (χ(1) = 4.20, p = 0.04).

Conclusion: Modification of naturalistic maladaptive memories during reconsolidation appears to be a viable treatment strategy for substance use and phobias/trauma disorders. However, high levels of heterogeneity and methodological variation limit the strength of conclusions that can be drawn from the reviewed studies at this stage.